Bis{8 2,6,6-trimethyl-4-oxo-cyclohexen-1-ylidene{9 -3,7,12,16-tetramethyl-2,6,8,10,12,16-octadecahexen-4,14-diyne

ABSTRACT

A method by which rhodoxanthin can be synthesized from 3ethylenedioxy- Beta -ionone as well as new and novel intermediates produced in the synthesis. Rhodoxanthin is a wellknown coloring agent for foodstuffs, including beverages, pharmaceutical and cosmetic preparations.

United States Patent [191 Surmatis et al.

[ BIS[2,6,6-TRIMETHYL-4-OXO- CYCLOHEXEN-l-YLIDENE]-3,7, 12,16-TETRAMETHYL-2,6,8,l0,l2,l6- OCTADECAHEXEN-4,l4-DIYNE [75] Inventors:Joseph Donald Surmatis; Armin Walser, both of West Caldwell, NJ.

[73] Assignee: Hofimann-La Roche Inc., Nutley,

[22] Filed: May 20, 1974 [21] Appl. No.: 471,268

Related US. Application Data [62] Division of Ser, No. 153,090, June 14,1971, Pat. No. 3,830,844, which is a division '0! Ser. No. 826,022, May19, 1969, Pat. No. 3,624,105, which is a division of Ser. No. 617,827,Feb. 23, 1967, Pat. No. 3,466,331.

[52] US. Cl 260/586 R Dec. 23, 1975 [51] Int. Cl. C07C 49/48 58 1 Fieldof Search 260/586 R [56] References Cited UNITED STATES PATENTS2,983,752 5/1961 Ruegg et al; 260/586 P X Primary ExaminerNormanMorgenstern Attorney, Agent, or Firm-Samuel L. Welt; Jon S. Saxe;William H. Epstein 1 Claim, No Drawings BIS[2,6,6-TRlMETHYL-4-0X0-CYCLOHEXEN-l- I YLlDENE]-3,7,12,16-TETRAMETHYL-2,6,8,10,l2,16DCTADECAHEXEN-4,l4-DIYNE CROSS REFERENCE TO RELATEDAPPLICATIONS 3,624,105, which in turn is a divisional application ofSer. No. 617,827 filed Feb. 23, [967, now U.S. Pat. 3,466,331.

BACKGROUND OF THE INVENTION,

This invention is d'irectedto' a method whereby rhodoxanthin can, besynthetically produced without the- 30, can be synthesized from thecompound of Formula l necessity for isolating rhodoxanthinor itsintermediates from their natural source.

SUMMARY or This lNv NTio This invention relates to thesynthesis ofrhodoxanthin from Rhodoxan t hin, which isfound in nature'in-theberriesRhodoxanthin which has the formulaf above through thepreparationbf aphosphoniurn salt intermediate of the formula:

W eMNRmZRaM wherein R R and R are straight 'andibran'ched chain ofevergreen trees such as Paxus Baccata, is widely *lower alkyl groupshaving from'l to 7 carbon atoms; or an aryl radical such as phenyl,naphthyl, etc.; or an aralkyl radical having from 7 to 15 carbon atomssuch as benzyl; and A is an anion of a mineral acid, e .g., Cl, Br, I,H80 etc. and an oxo aldehyde intermediate used as a coloring materialfor foodstuffs and beverages as well as pharmaceutical and cosmeticpreparations. Rhodoxanthin imparts to foodstuffs, pharmaceutical andcosmetic preparations a red coloration. In the past rhodoxanthin hasbeen produced by isolating this mate: rial from its natural source suchas from the berries of evergreen plants. This procedure has provenextremely disadvantageous due to the fact that rhodoxanthin occurs onlyin small amounts in these berries. Therefore, a great quantity of theseberries must be utilized in order to isolate a small amount ofrhodoxanthin. Additionally, the process whereby rhodoxanthin is isolatedfrom the berries of green plants has proven extremely cumbersome anduneconomical. Up until the present time there has .been no procedure fordirectly chemically;synthesizing rhodoxanthin without isolatingrhodoxanthin er -precursors of rhodoxanthin from their natural source.Therefore,-it has been long desired in the art to provide a methodforchemically synthesizing rhodoxanthin was to eliminate the necessityof isolating rhodoxanthin or its precursors from its natural source.

of the formula:

but) 7 ln accordaneewith thisfinventiomthe intermediates of Format-.111andjlV above are reacted in the pres- 65. ence of a strong alkali and'the reaction product is selec-- v tively reduced and hydrogenatedat thetriple bond to form rhodoxanthin.

In accordance with another embodiment of this invention, rhodoxanthincan be synthesized by the condensationof'an intermediate of the formula:

wherein R R R and A are as above with an intermediate of the formula:

VWA

in the presence of an inert organic solvent.

By means of the above processesv of this invention,

rhodoxanthin can be chemically synthesized simply and economicallywithout the necessity for isolating the rhodoxanthin from its naturalsource.

The term lower alkyl" as used throughout the specification denotes analkyl radical containing from 1 to 7 carbon atoms such as methyl, ethyl,butyl, propyl, isopropyl, etc.

DETAILED DESCRIPTION OF THE INVENTION The phosphonium salt compound ofFormula Ill above is reacted in accordance with this invention with the0x0 aldehyde compound of Formula IV to produce an acetylenic dioxocompound of Formula VII:

meta-l hydroxide in a lower alkanol, e.g.', KOH in methanol. Otherstrong bases which can be utilized include aryl or alkyl. group I-Ametallo organic compounds wherein lithium, sodium, potassium, rubidium,cesium,

and francium are the preferred metallo moieties and wherein thepreferred alkyl moieties are the lower alkyl groups and the preferredaryl moieties are phenyl and lower alkyl-substituted phenyl groups,withphenyl lithium and butyl lithium being the'preferred metallo organics.In carrying out this reaction, temperature and pressure are not criticaland this reaction can be carried out at room temperature and elevated orreduced pressure. Furthermore, in carrying out this reaction, it

, is generally preferred to react one mole of the compound of FormulaIII above with one mole of the compound of Formula IV above. However, ifdesired a molar excess of the compound of Formula III above or thecompound of Formula IV above can be employed.

The acetylenic compound of Formula VII above can be converted torhodoxanthin by partially hydrogenating the compound of Formula VIIabove at the triple bond to reduce all of the-triple bonds containedtherein to double bonds. The reduction of the compounds of Formula VIIabove to rhodoxanthin can be effected by catalytichydrogenation in thepresence of a catalyst which selectively reduces only the triple bond(acetylene linkage) to a double bond. For example, compounds of FormulaVII above can be catalytically hydrogenated, in an inert solvent such asethyl acetate, toluene or petroleum ether, in the presence of aselective hydrogenation catalyst, e.g., a palladium-lead catalyst in thepresenceof quinoline, of the type disclosed in the publication HelveticaChimica Acta, 35, 446 (1952).

The phosphonium salt of Formula III above can be synthesized from acompound of Formula I above by means of the following reaction scheme:

cn (in (VIII) (c) Rg-i-Rl nesium chloride, ethyl magnesium bromide,phenyl magnesium iodide, chlorophenyl lithium, etc. In carrying out thecondensation reaction of step (a), temperature and pressure are notcritical and the reaction can be carried out at room temperature and atatmospheric isopropenyl ethynyl carbinol wherein R R R and A are asabove.

The condensation reaction of the compound of Formula I above withisopropenyl ethynyl carbinol is carried out in an inert solvent in thepresence of a Grignard reagent. Any conventional inert organic solventcan be utilized as the reaction medium in accordance with thisinvention. Included among the solvents suitable for the purpose of thepresent invention are hydrocarbons such as benzene, toluene, Xylene, andthe like; ethers such as tetrahydrofuran, diethyl ether, dioxane, andthe like, or any other suitable solvent. Any conventional Grignardreagent may be utilized in the condensation reaction of the compound ofFormula I above with isopropenyl ethynyl carbinol. Typical Grignardreagents include lower alkyl metallic halides. Among the many Grignardreagents that can be utilized in accordance with this invention areincluded ethylmagpressure. If desired, the reaction of step (a) can becarried out at reduced temperatures and/or reduced or elevated pressure.Generally, it is preferred to carry out the reaction of step (a) at thereflux temperature of the solvent.

The compound of Formula VIII above is converted to the compound ofFormula IX above by dehydration, due to the instability of the tertiaryhydroxy group, and by hydrolysis. Any conventionaldehydration andhydrolysis procedure can be utilized to hydrolyze and to remove thetertiary hydroxy group from the compound of Formula VIII to convert itinto the compound of Formula IX above. This can be accomplished bytreating the compound of formula VIII above with a dilute acid such assulfuric acid, paratoluenesulfuric acid, hydrochloric acid, hydrobromicacid; etc. Generally, in utilizing an acid, no more than 10 parts byweight,

preferably from about 0.1 to 7.0 parts by weight of the acid should beutilized, based upon the weight of the reaction medium. When treating acompound of formula VIII with dilute acid simultaneously with thedehydration the ketalized oxo group is hydrolyzed to an oxo group. Ifdesired, the dehydration reaction can be carried out by heating thecompound of Formula VI" in the presence of a water-binding agent. Insuch a case a separate hydrolysis step is required for converting theketalized oxo grourp to an oxo group. Water-binding agents are meant toinclude such substances as have a marked tendency to add on waterphysically or in complex form, also in the presence of organic solvents.It is known to any worker in the art which agents are to be used in eachparticular case.

In step (c), the compound of Formula IX above is coverted into thecompound of Formula III by means of reacting the compound of Formula IXabove with a phosphine of Formula X above in the presence of a protondonor or with an acid addition salt of a phosphine of Formula X above.Proton donors which can be employed in the above process includeinorganic acids, such as the hydrohalic acids (especially hydrochloricacid) or sulfuric acid. Moreover, all acids which form acid additionsalts with phosphines of Formula X (e.g., strong organic acids such asbenzenesulfonic acid or trichloroacetic acid) as well as thosespecifically named R 0- CI-I-CH 1-1-1 CH-CEC-C-CH= above, can beemployed. When an acid addition salt of the phosphine of Formula X aboveis utilized, the acid used to form the acid addition salt can be anystrong acid such as the mineral acids and the strong organic acids suchas the sulfonic acids, e.g., benzene and toluenesulfonic acid, etc. Thereaction of step (c) is carried out in the presence of an inert solvent,such as, for example, a lower alkanol such as methanol or ethanol.Generally, this reaction is carried out under substantially anhydrousconditions, that is, the reaction medium or solvent should not containmore than 10 percent by weight of water. In carrying out the reaction ofstep (c), temperature and pressure are not critical. Hence, the reactionof step (c) can be carried out at room temperature or elevated orreduced pressure. In this manner, a compound of Formula III above isformed.

The 0x0 aldehyde compound of Formula VI above is prepared from thecompound of Formula I above by means of the following reaction scheme:

wherein R R and R are lower alkyl groups.

The compound of Formula XI above is condensed with the compound ofFormula I above in the presence of a Grignard agent to produce thecompound of Formula XII. This Grignard condensation reaction as in step(d) is carried out in the same manner and utilizing the same generalconditions as was utilized in the condensation reaction in step (a).Generally, this condensation reaction is carried out by condensing onemole of the compound of Formula XI with one mole of the compound ofFormula I above in the presence of a Grignard agent such as thosementioned hereinbefore. This condensation reaction is carried out byutilizing an inert organic solvent as the reaction medium. The compoundof Formula XII thus obtained is then hydrolyzed in an acid medium toproduce the compound of Formula IV above. This hydrolysis proceeds withthe simultaneous splitting off of alcohol and water from the molecule soas to convert the two terminal ether groups to an aldehyde group whileforming an additional dou- In accordance with another embodiment of thisinvention, rhodoxanthin can be directly synthesized by condensing onemole of a compound of Formula V above with one mole of a compound ofFormula VI above. The conditions utilized in condensing the compound ofFormula V above with the compound of Formula VI above are the same thatare utilized in the condensation of the compound of Formula III abovewith that of Formula IV above to produce a compound of Formula VII.

The compound of Formula V above can be produced from the compound ofFormula IX above by means of the following reaction scheme:

l l (XIII) 0 on a (i) (RlRaRanP Mwmmm ble bond within the compound ofFormula XII above.

In the above scheme R R R and A have the same Furthermore, the dioxoradical is converted to a keto 45 meaning hereinbefore given.

group and the tertiary hydroxy group is removed from the molecule. Thisreaction step can suitably be carried out in the presence of awater-soluble, non-volatile organic or inorganic acid such asparatoluenesulfonic acid, acetic acid, propionic acid, oxalic acid,sulfuric acid, phosphoric acid, or a water-soluble acid salt such aszinc chloride. Acetic acid with the addition of a little water ispreferred. The hydrolysis is conveniently carried out in the presence ofan added sodium salt, preferably sodium acetate. The reaction ispreferably carried out with exclusion of oxygen and the addition of anantioxidant, e.g., hydroquinone. The reaction is bestcarried out underconditions, wherein thealcohol formed by the reaction distills off fromthe reaction mixture. A water-miscible solvent can be employed such asdioxane, tetrahydrofuran, ethylene glycol, dimethyl: ether, etc.,inorder to obtain a homogeneous reaction mixture. Any conventionalhydrolysis conditions can be utilized in carrying out this reaction. Incarrying out this hydrolysis reaction, it is preferable to use elevatedtemperatures. However, this reaction will proceed at room temperatureand the alcohol that formes during the reaction can be separated laterby washing.

reaction with a phosphonium salt of Formula X above in the presence of aproton donor or with the acid addition salt of the phosphonium compoundof Formula X above. This reaction is carried out in the same manner andutilizing the same conditions as in the conversion of the compound ofFormula IX above to the compound of Formula III above in step (c).

The compound of Formula VI above is prepared from the compound ofFormula IV above by selectively hydrogenating the triple bond in thecompound of Formula IV above to a double bond. This selectivehydrogenation can be carried out in the same manner outlined with regardto the conversion of the compound. of

Formula VII above to rhodoxanthin.

The ionone compound of Formula I above which is utilized to prepare theintermediates in accordance with this invention can be synthesized bythe following reaction scheme: 1

mesityl oxide CHzOH acetoacetic ester (XVIII) wherein R and R are loweralkyl groups.

The condensation, as in step (k), of mesityl oxide and acetoacetic acidester to form the lower alkyl ester of3,5,5-trimethyl-2-cyclohexen-l-one-4-carboxylic 'acid carrying'out thisreaction, any conventional acid cata- I lyst can be utilized. The acidcondensing agent or catalyst which can be utilized in accordance withthis invention are preferably strong acids such as the mineral acids,Lewis acids, e.g., boron trifluoride, zinc chloride, etc., stronglyacidic organic acids such as toluenesulfonic acid, oxalic acid,trichloroacetic acid, etc. In carrying out this condensation reaction,the reflux tem- (XIX) perature of the solvent medium could be utilized.This temperature can vary from 50C. to C. depending upon the solventutilized. The conversion'of the ester compound of Formula XV above tothe etherified carboxylicacid ester compound of Formula XVI above iscarried out by treating the compound of Formula XV above with a loweralkyl triester of formic acid in the presence of an inorganic acid ormineral acid. This reaction is preferably'carried out in an organicsolvent. Any of the aforementioned solvents can be utilized in carryingout this reaction. Any of the conventional mineral acids such assulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid,etc., can be utilized in carrying out this reaction. Typical esters offormic acid which can be utilized in carrying out this reaction includetriethylorthoformate, trimethylortho- 13 formate,triisopropylorthoformate, etc. In carrying out this reaction,temperature and pressure are not critical and the conversion of thecompounds of Formula XV above to the compounds of Formula XVI above canbe effected at room temperature and at atmospheric pressure or atelevated or reduced temperatures and/or elevated or reduced pressure.

The ether compound of'FormulaXVI above is converted to thedioxycarboxylic acid ester of Formula XVII above by treating compoundsof Formula XVI 'above with ethylene glycol at elevated temperatures inan inert organic solvent medium. Any of the conventional inorganicsolvents such as the aforementioned solvents can be utilized in carryingout this reaction. This reaction is carried out by utilizing an acidcatalyst such as any of the aforementioned acid catalysts .or condensingagents. In carrying out this reaction, temperatures of above atemperature of about 60 should be utilized. The highest temperaturewhich can be utilized in carrying out this reaction will depend upon thereflux temperature of the reaction medium. The ethylene glycol which isutilized in this reaction should be present so as to provide one mole ofethylene glycol per mole of the compound of Formula XVI above.

Upon treatment of the compound of Formula XVII above with an alkalimetal aluminum hydride reducing agent such as lithium aluminum hydride,sodium aluminum hydride, etc., the ester radical on the compound ofFormula XVII above is reduced to a hydroxy radical to produce thecorresponding dioxyhydroxy compound of Formula XVIII above. Thereduction with the alkali metal aluminum hydride reducing agent ispreferably carried out under anhydrous conditions in the presence of aninert organic solvent such as any of the aforementioned organicsolvents. The reaction is suitably carried out at room temperature.However, temperatures of from about C. to about 80C. can be utilized incarrying out this reaction.

The dioxyhydroxy compound of Formula XVIII above can be converted to thecorresponding dioxyaldehyde compound of Formula XIX above by means ofoxidation. Any conventional oxidizing technique can be utilized tooxidize the compounds of Formula XVIII above to the compounds of FormulaXIX above. The dioxyaldehyde compound of Formula XIX above can beconverted to the ionone compounds of Formula I above by means ofcondensing one mole of the compound of Formula XIX above with one moleof acetone as in step (p). This condensation reaction should be carriedout in the presence of a strong base, preferably an alkali metalhydroxide such as potassium hydroxide, sodium hydroxide, sodiummethoxide, lithium hydroxide, calcium hydroxide, etc. In carrying outthe condensation reaction of step (p) temperature and pressure are notcritical so that the reaction can be carried out at room temperature.However, if desired, elevated or reduced temperatures can be utilized aswell as elevated or reduced pressures. This reaction is carried out inan organic solvent media, preferably acetone.

The following examples illustrate the invention. In the examples, thepetroleum ether utilized boiled at a range of 60C. to 80C. Alltemperatures utilized in the following examples are in degreescentigrade.

EXAMPLE 1 3 ,5 ,5-Trimethyl-2-Cyclohexenl -on-4-Carboxylic Acid MethylEster A mixture of 2.6 kg. of methyl acetoacetate, 2.75 kg. of mesityloxide, 400 g. of zinc chloride, 2 l. of heptane, and 2 l. of benzene wasrefluxed for 5 days. The water formed during the reaction wasazcotropically distilled off and collected in a separator. A brown oilyproduct remained in the flask. The oily product was then washed withwater, sodium bicarbonate solution, and again with water. The oil whichremained after washing was dried over calcium chloride and theheptane-benzene solvent removed under vacuum. The remaining oil wasdistilled under high vacuum over a packed column. From the distillationthere was obtained first a forecut of unreacted ethyl acetoacetate andmesityl oxide, a second fraction of isophorone by product and finallycrude 3,5,5-trimethyl-2-cyclohexen-l-on-4-carboxylic acid methyl esterwith a boiling range of 95-l04 at 0.40.6 mm.Hg. This crude materialiwasutilized for all experiments without further purification. Pure 3,5,5-trimethyl-Z-cyclohexen-l-on-4-carboxylic acid methyl ester was obtainedby chromatographic separation on silica gel G (finely divided powderedSilica containing trace amounts of calcium sulfate), using petroleumether and ethyl ether in a volume ratio of 7 to 3.

EXAMPLE 2 7,9,9-Trimethyl-l ,4-Dioxaspiro[4,5 ]dec-7-en-8-CarboxylicAcid Methyl Ester 800 g. of crude 3,5,5-trimethyl-2-cyclohexen-l-on-4-carboxylic acid methyl ester and 720 g. of triethyl orthoformate weremixed with L5 1. of anhydrous ethanol containing 4 ml. of sulfuric acid.After standing for 4 hours at room temperature, the dark blue solutionwas poured onto petroleum ether over a sodium bicarbonate solution. Theether layer was washed twice with water, dried over sodium sulfate andconcentrated by removing all of the ether solvent. The resulting darkresidue was distilled over a vigreux column under high vacuum to yield2,6,6-trimethyl-4-ethoxy-l ,3- cyclohexadien-l-carboxylic acid methylester.

' 670 g. of crude 2,6,6-trimethyl-4-ethoxy-l ,3-cyclohexadien-l-carboxylic acid methyl ester and I g. of ethylene glycolwere heated in 3 l. of benzene in the presence of 3 g. of p-toluenesulfonic acid. The reaction was stopped after 1.5 l. of benzene haddistilled over. The cold solution was washed with sodium bicarbonatesolution and water, dried, and evaporated. The remaining oil wasdissolved in l l. of petroleum ether and crystallized at l0. A yield of320 g. (m.p. 67-69) was obtained after recrystallization from petroleumether. This product was identified as 7,9,9- trimethyl-l,4-dioxaspiro[4,5 ldec-7-en-8-carboxylic acid methyl ester.

EXAMPLE 3 7,9,9-Trimethyll ,4-Dioxaspiro[4,5 ]dec-7 en-8- Methanol Asolution of 300 g. of7,9,9-trimethyl-l,4-dioxaspiro[4,5]dec-7-en-8-carboxylic acid methylester in l l. of ether was slowly added to a stirred suspension of 50 g.of lithium aluminum hydride in l l. of ethyl ether. During the addition,which required 1 hour, the temperature was kept between 15 and 20. Itwas then en-8-methanol.

EXAMPLE 4 7 ,9,9-Trimethyl-l ,4-Dioxaspiro[4,5]dec-7-en-8-Carboxaldehyde 3 kg. of maganese dioxide was added in fourportions over a period of 2 days to a solution of 150 g. of crystalline7 ,9,9-trimethyl-l ,4-dioxaspiro[4,5 ]dec-7-en-8- methanol in 3 l. ofmethylene chloride. After the mixture was stirred under nitrogen for anadditional day, the oxidation was complete according to a determinationby thin layer chromatography. Filtration and evaporation of the solventyielded the crude product which was used for the next step withoutfurther purification. A small portion of this product was purified byvacuum distillation. This product was identified as 7,9,9- trimethyl-l,4-dioxaspiro [4,5 ]dec-7-en-8-carboxaldehyde.

EXAMPLE 5 3-Ethylenedioxy-B-lonone A mixture of 120 g. of crude7,9,9-trimethyl-l ,4- dioxaspiro [4,5]dec-7en-8-carboxaldehyde, 500 ml.of acetone, and 60 ml. of 10% aqueous solution of potassium hydroxidewas refluxed under nitrogen for 16 hours. Most of the solvent wasremoved under vacuum and the residue was diluted with water andextracted with petroleum ether leaving an oil layer. The oil layer waswashed neutral with water, dried over sodium sulfate and concentrated.The residue was distilled under reduced pressure over a vigreux column.The fraction boiling between ll5 and 140 at 0.3 to 0.7 mm. Hg.crystallized from petroleum ether at lO to 20". Recrystallization frompetroleum ether yielded 60 g. of the 3ethylenedioxy-B-ionone.

EXAMPLE 6 2,6-Dimethyl-8-(4-Oxo-2,6,6-Trimethyl-2-Cyclohexenylidene l,6-Octadien-4-yn-3-ol 9.6 g. of isopropenyl-ethynyl-carbinol was droppedinto a suspension of ethyl magnesium bromide in 200 ml. of ether(prepared from 6.1 g. of magnesium and 27 g. of ethyl bromide) andrefluxed for 45 min. 20 g. of 3-ethylenedioxy-B-ionone in 100 ml. ofethyl ether was then added to the mixture, which was cooled with icewater. After stirring for 1 hour at room temperature, the reactionmixture was quenched with water forming a magnesium hydroxideprecipitate. The precipitate dissolved in the reaction media by additionof 5% sulfuric acid. Two layers were formed, an aqueous layer and anether layer which contained the product. The ether layer was separatedfrom the aqueous layer. The separated ether layer was washed with water,dried and concentrated by removing the solvent to yield the crudecompound of formula Vlll above.

This crude compound of formula VI" above was refluxed for 2 hours, withstirring, in 100 ml. of methylene chloride and 20 ml. of 5% aqueoussulfuric acid. The methylene chloride solution was washed neutral, driedover sodium sulfate and concentrated by distilling off the solvent.Crude 2,6-dimethyl-8-(4-oxo-2,6,6-trimethyl-2-cyclohexenylidene)-1,6-octadien-4-yn-3-ol was obtained. Thiscrude product was purified by chromatography on 300 g. of silica gel Gusing petroleum etherethyl ether in volume ratio of l to 1.

EXAMPLE 72,6-Dimethyl-8-(4-Oxo-2,6,6-Trimethyl-2-Cyclohexenylidene)-2,6-Octadien-4-yneTriphenylphosphonium Bromide 9 g. of triphenylphosphonium bromide wasadded to a solution which consisted of 5 g. of purified 2,6-dimethyl-8-(4-oxo-2,6,6-trimethyl-2-cyclohexenylidene)-l,6-octadien-4-yn-3-ol and 200 cc. of benzene. After standing at roomtemperature for l6 hours, the solution was washed three times withwater, dried over sodium sulfate, and concentrated to remove solvent.The residue was dispersed in ethyl acetate to remove triphenylphosphineThe separated solid crystallized partially from ethyl acetatemethanol toyield crystalline material. This material was identified as2,6-dimethyl-8-(4-oxo-2,6,6-trimethyl-2-cyclohexenylidene)-2,6-octadien-4-ynetriphenylphosphonium bromide.

EXAMPLE 8 4,8-Dimethyll 0-(4-Oxo-2,6,6-Trimethyl-2-Cyclohexenylidene)-2,4,8-Decatrien-6-ynal 24 g. of 4-methyl-l ,1,3triethoxy-4hepten-6-ynewas dropped into a suspension of ethyl magnesium bromide prepared from2.7 g. of magnesium and 14 g. of ethyl bromide in ml. of ethyl ether.After 30 min. of reflux, 20 g. of 3-ethylenedioxy-B-ionone in 100 ml. ofether was added at 5. The reaction was then stirred for 2 hours at roomtemperature and quenched with water forming two layers, i.e., a waterand an ether layer which contained compound of formula Xll above. Thedecanted ether layer was dried and concentrated to remove ethyl ether.The compound Xll which formed a residue was heated on the steam bath for3 hours with 250 ml. of acetic acid, 30 ml. of water and,

40 g. of sodium acetate forming a dark solution. The

EXAMPLE 9 10,1 ll 0,l l 'Bis-Dehydro-Rhodoxanthin[trans- 3,7,1 2,]6-tetramethyll ,l 8-bis(2,6,6-trimethyl-4-oxo- Z-cyclohexenl -ylidene)2,6,8,10,l2,16-octadecahexane-4,l4-diyne] l g. of sodium methoxide wasadded slowly to a stirred solution of 2.6 g. of 2,6-dimethyl-8-(4-oxo-2,6,6-trimethyl-2-cyclohexenylidene)-2,6-octadien-4- ynetriphenylphosphonium bromide and 1.2 g. of 4,8-dimethyl-l0-(4-oxo-2,6,6-trimethyl-2-cyclohex- EXAMPLE l4-Cis-2,6-Dimethyl-8-(4-Oxo-2,6,6-Trimethyl-2- Cyclohexenylidene )-l,4,6-Octatrien-3-ol EXAMPLE 1 l2,6-Dimethyl-8-(4-Oxo-2,6,6-Trimethyl-Z-Cyclohexenylidene)-2,6,8-OctatrienTriphenylphosphonium Bromide 4 g. of pure4-cis-2,6-dimethyl-8-(4-oxo-2,6,6- trimethyl-2-cyclohexenylidene l,4,6-octatrien-3-ol and 7 g. of triphenylphosphonium bromide weredissolved in 200 cc. of methylene chloride and allowed to react for 16hours. The solution was then washed 4 times with water, dried andconcentrated to remove solvent. The residue was dispersed in 200 cc. ofethyl Ill 18 acetate, and the insoluble material was filtered off anddissolved in an ethyl acetate-methanol mixture where it crystallizedpartially. This product was identified as2,6-dimethyl-8-(4-oxo-2,6,6-trimethyl-2-cyclohexenylidene)-2,6,8-octatrientriphenylphosphonium bromide.

EXAMPLE l2 4,8-Dimethyll0-(4-Oxo-2,6,6-Trimethyl-2-Cyclohexenylidene)-2,4,6,8-Decatetraenal 2 g.of pure 4,8-dimethyl-10-(4-oxo-2,6,6-trimethyl-Z-cyclohexenylidene)-2,4,8-decatrien-6-ynal in ml. of benzene washydrogenated in the resence of 0.5 g. of Lindlar catalyst and 0.5 ml. ofa 1 0 solution of quinoline in acetone. After consumption of 240 ml. ofhydrogen, which took place within 2 5% hours, the suspension wasfiltered and concentrated. The residue crystallized only partially afterchromatography on 200 g. of silica gel G with benzene ethyl ether in avolume ratio of 3:2.

EXAMPLE l3 Rhodoxanthin 0.5 g. of 10,1 l,l0',ll'-bis-dehydro-rhodoxanthin in 50 ml. of benzene was hydrogenated in thepresence of 100 mg. of Lindlar catalyst and 0.1 ml. ofa 1% solution ofquinoline in acetone. After ml. of hydrogen had been consumed (within 2hours), the filtered solution was concentrated. The residue was placedin a sealed tube with 2.5 ml. of benzene and 5 ml. of heptane and heatedon the steam bath for 24 hours. During this isomerization, rhodoxanthincrystallized out in dark violet crystals. The rhodoxanthin wasrecrystallized from benzeneheptane mixture.

0.2 g. of 4,8-dimethyl-l0-(4-ox0-2,6,6-trimethyl'2-cyclohexenylidene)-2,4,6,8-decatetraenal and 0.35 g. of2,6-dimethyl-8-(4-oxo-2,6,6-trimethyl-2'cyclohexenylidene)-2,4,6-octatrientriphenylphosphonium bromide were dissolved in 6 ml. of methanol andtreated with 0.2 g. of sodium methoxide at 0 for 4 hours. Theprecipitated dark violet solid was collected and recrystallized frombenzene methanol to yield rhodoxanthin.

We claim:

1. A compound of the formula:

1. A COMPOUND OF THE FORMULA: